The Immunological Response

Immunological responses are associated with macrophages or dendritic cells and two subpopulations of lymphocytes, B-cells and T-cells.

Under antigenic stimulus, B-lymphocytes become transformed into antibody-secreting plasma cells. The plasma cells synthesize large amounts of immunoglobulins (antibodies) which will react stereochemically with the stimulating antigen.

Under antigenic stimulus, pre T-lymphocytes differentiate into several classes of effector T cells which are committed to various activities upon recognition of the specific antigen that induced their formation. T cells have many activities relevant to immunity including (1) mediation of the B-cell response to antigen; (2) ability to recognize and destroy cells bearing foreign Ag on their surface; and (3) production of a variety of diffusible compounds called cytokines and/or lymphokines, which include substances that are activators of macrophages, mediators of inflammation, chemotactic attractants, lymphocyte mitogens, and interferon. Cytokines and lymphokines are molecules (peptides, proteins) produced by cells as a means of intercellular communication. Generally, they are secreted by a cell to stimulate the activity of another cell.

The overall aspects of the induction of an immunological response (AMI and CMI) are shown in the following schematic diagram.
 

Three important features of an immunological response relevant to host defense and/or "immunity" to pathogenic microorganisms are:

1. Specificity. An antibody or reactive T-cell will react specifically with the antigen that induced its formation; it will not react with other antigens. Generally, this specificity is of the same order as that of enzyme-substrate specificity or a receptor-ligand interaction. However, cross-reactivity is possible. The specificity of the immunological response is explained on the basis of the clonal selection hypothesis: during the primary immune response, a specific antigen selects a pre-existing clone of specific lymphocytes and stimulates exclusively its activation, proliferation and differentiation.

2.  Memory. The immunological system has a "memory". Once the immunological response has reacted to produce a specific type of antibody or reactive T-cell, it is capable of producing more of the antibody or activated T-cells rapidly and in larger amounts. This is referred to as a secondary or memory response.

3. Tolerance. An animal generally does not undergo an immunological response to its own (potentially-antigenic) components. The animal is said to be tolerant to self-antigens. This ensures that under normal conditions, an immune response to "self" antigens (called an autoimmune response) does not occur. Autoimmune responses are potentially harmful to the host. Tolerance is brought about in a number of ways, but basically the immunological system is able to distinguish "self" antigens from "non-self" (foreign) antigens; it will respond to "non-self" but not to "self". Sometimes in an animal, tolerance can be "broken", which may result in an autoimmune pathology.

The Two Types Adaptive Immunity: AMI and CMI

Antibody-mediated immunity (AMI) is the type of adaptive immunity that is mediated by soluble host proteins called antibodies or immunoglobulins. Because it is largely due to the presence of circulating antibody molecules in the serum, is also called circulating immunity or humoral immunity.

If a naive (unstimulated) B cell encounters an antigen, it is stimulated to develop into a plasma cell which produces the antibodies that will react with the stimulating antigen. They also develop into clones of identical reactive B-cells called memory B-cells.

Antibodies (Ab) are proteins (globulins) produced in response to an encounter with an antigen (Ag). There are several classes or types of antibodies (and subclasses of the types), but all antibodies are produced in response to a specific antigen react stereochemically with that antigen and not with other (different) antigens. An animal has the genetic capacity to produce specific antibodies to thousands of different antigens, but does not do so until there is an appropriate (specific) antigenic stimulus. Due to clonal selection, the host produces only the homologous antibodies that will react with that antigen. These antibodies are found in the blood (plasma) and lymph and in many extravascular tissues. They have a various roles in host defense against microbial and viral pathogens as discussed below.

Cell-mediated immunity (CMI) is the type of adaptive immunity that is mediated by specific subpopulations of T-lymphocytes called effector T-cells. In non immune animals precursor T-cells (pT cells) exist as "resting T cells". They bear receptors for specific antigens. Stimulation with Ag results in their activation. The cells enlarge, enter into a mitotic cycle, reproduce and develop into effector T-cells whose activities are responsible for this type of immunity. They also develop into clones of identical reactive T-cells called memory T-cells.

The biological activities of the antibody-mediated and cell-mediated immune responses are different and vary from one type of infection to another. The AMI response involves interaction of B lymphocytes with antigen and their differentiation into antibody-secreting plasma cells. The secreted antibody binds to the antigen and in some way leads to its neutralization or elimination from the body. The CMI response involves several subpopulations of T lymphocytes that recognize antigens on the surfaces of cells. TH cells (CD4⁺) respond to antigen with the production of lymphokines. A distinction between TH1 cells and TH2 is based on their lymphokine profiles. TH2 cells have previously been referred to as T-helper cells because they provide lymphokines (e.g. IL-2 and IL-4) which activate T cells and B cells at the start of the immune response. TH1 cells were formerly known as delayed type hypersensitivity cells (TDTH) because of their role in this allergic process. Tc cells (CD8⁺) or cytotoxic T lymphocytes (CTLs) are able to kill cells that are showing a new or foreign antigen on their surface (as virus-infected cells, or tumor cells, or transplanted tissue cells).

AMI and CMI are discussed separately in more detail below.

Membrane receptors on B-cells and T-cells

The nature of the membrane receptors for antigen on B-cells and T-cells is fairly well understood. Each B cell has approximately 10⁵ membrane-bound antibody molecules (IgD or IgM) which correspond in specificity to the antibody that the cell is programmed to produce. Each T cell has about 10⁵ molecules of a specific antigen-binding T cell receptor (TCR) exposed on its surface. The TCR is similar, but not identical, to antibody. In addition, T cell subsets bear some distinguishing surface markers, notably CD4 or CD8. T cells bearing CD4 always recognize antigens in association with class II major histocompatability complex (class II MHC) proteins on the surfaces of other cells. CD4⁺ T lymphocytes generally function as T helper cells or in modulation of immune responses. T cells bearing CD8 ( CD8⁺ ) always recognize antigen in association with class I MHC proteins and typically function as cytotoxic T cells. The important markers, actions and interactions of T cells, B cells and Antigen Presenting Cells (APC) are illustrated below.

Figure 4. Receptor interactions between B cells, T cells and Antigen Presenting Cells (APC)